Integrated of multi-omics and molecular docking reveal PHGDH, PSAT1 and PSPH in the serine synthetic pathway as potential targets of T-2 toxin exposure in pig intestinal tract.

T-2 toxin (T-2) with a molecular weight of 466.52 g/mol is an inevitable mycotoxin in food products and feeds, posing a significant threat to human and animal health. However, the underlying molecular mechanisms of the cytotoxic effects of T-2 exposure on porcine intestinal epithelial cells (IPEC-J2) remain unclear. Here, we investigated the cytotoxic effects of T-2 exposure on IPEC-J2 through the detection of cell viability, cell morphology, mitochondrial membrane potential, ROS, apoptosis and autophagy. Further transcriptomic and proteomic analyses of IPEC-J2 upon T-2 exposure were performed by using RNA-seq and TMT techniques. A total of 546 differential expressed genes (DEGs) and 269 differentially expressed proteins (DEPs) were detected. Among these, 24 common DEGs/DEPs were involved in IPEC-J2 upon T-2 exposure. Interestingly, molecular docking analysis revealed potential interactions between T-2 and three key enzymes (PHGDP, PSAT1, and PSPH) in the serine biosynthesis pathway. Besides, further experimental showed that PSAT1 knockdown exacerbated T-2-induced oxidative damage. Together, our findings indicated that the serine biosynthesis pathway including PHGDP, PSAT1, PSPH genes probably acts critical roles in the regulation of T-2-induced cell damage. This study provided new insights into the global molecular effects of T-2 exposure and identified the serine biosynthesis pathway as molecular targets and potential treatment strategies against T-2.